Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations

Abstract

The purpose of this study was to investigate the association among matrix metalloproteinases (gelatinases A and B, stromelysin-3 (ST3) and matrilysin) mRNAs expressed in primary breast carcinomas and standard prognostic parameters and clinical outcome. mRNA levels were determined by Northern analysis in samples of 81 breast cancer patients (median follow-up, 40 months) and 27 samples of uninvolved adjacent breast tissue. Proteases were expressed by the majority of the tumors and normal breast tissues examined. ST3, gelatinase A and matrilysin mRNAs were more often expressed at high levels in carcinomatous than in normal breast tissues. Differences in the distribution of gelatinase B mRNA were not found. However, paired normal tissues generally produced weaker signals when compared to matched tumor samples. Univariate analysis showed no significant association of gelatinase A and matrilysin mRNAs with the classical prognostic markers (age, menopausal status, stage, size, nodal status, vascular infiltrate, necrosis, steroid receptors, metastasis and survival). Overexpression of ST3 was more frequently found in tumors of post-menopausal women (P < 0.022). Elevated expression of gel B mRNA was associated with the presence of vascular infiltrate (P < 0.026), necrosis (P < 0.039), PR negative tumors (P < 0.014) and inversely correlated to the number of survivors (P < 0.021). Multivariate analysis including 68 patients for whom all information was available indicated that neither stromelysin correlated significantly with pathological, clinical or biochemical features. High levels of gelatinase A and B mRNAs were inversely associated with the number of survivors. Our findings suggest that measurements of gelatinase A and B mRNAs expression in breast carcinoma may help to identify patients with an aggressive form of the disease.

Prognostic significance of matrix metalloproteinase‐7 in epithelial ovarian cancer and its relation to β‐catenin expression

“…Previous studies on breast and lung cancers have revealed no significant correlation between the expression of MMP-7 and standard prognostic factors. 28,29 By contrast, in colorectal cancer, MMP-7 positivity in cancer cells correlates signifi- cantly with the depth of invasion, advanced Duke's stage and lymphatic and distant metastasis. 30,31 Indeed, several studies on gastrointestinal carcinomas suggest that high MMP-7 expression in cancer cells predicts shortened survival.…”

Gelatinase-mediated migration and invasion of cancer cells

“…In melanoma, increased expression of MMP-9 is found in the early steps, but at a later stage the opposite is true (van den Oord et al, 1997). In breast and colon cancer MMP-9 expression has been correlated with both increased and decreased survival and formation of distant metastasis (Pacheco et al, 1998;Scorilas et al, 2001;Takeha et al, 1997;Zeng et al, 1996). The current view is that the gelatinases and other MMPs are needed at multiple stages during the tumor progression and different tumors may utilize different MMPs.…”

Overexpression of matrix-metalloproteinase-9 in human breast cancer: a potential favourable indicator in node-negative patients

“…With regard to MMP-9, many reports show that it is expressed in breast cancer tissue, but there are conflicting results regarding the identity of the cells that express this protease (Visscher et al, 1994;Heppner et al, 1996;Nielsen et al, 1996aNielsen et al, , 1997. Although the expression of MMP-9 in breast tumour tissue has been examined by different methods, namely ELISA (Duffy et al, 1995), northern blotting (Pacheco et al, 1998), zymography (Rha et al, 1997(Rha et al, , 1998, in situ hybridization (Nielsen et al, 1997) and immunohistochemistry (Nielsen et al, 1997) but to the best of our knowledge, survival analysis connecting MMP-9 expression with disease outcome has not been performed with enough samples to produce statistically significant results.…”